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Transcranial focused ultrasound (tFUS) is gaining wider acceptance in a range of therapeutic applications for the treatment of brain disorders. It represents a promising noninvasive modality for providing therapeutic ablative treatments as well as subtherapeutic treatments for brain conditions. Advances in image guidance modalities, especially MRI, have impacted progress and led to increased interest in tFUS-based therapies. While these advances have proved to be essential to improve tFUS applications, the precise delivery of localized tFUS beams is still difficult due to phase aberrations and attenuation of the beams by the skull. Compensating for these distortions requires refocusing techniques for ultrasound beams. Based on the advent of dual-mode ultrasound array (DMUA) systems and their ability to operate in imaging and therapy modes in real time, we developed a realtime image-based refocusing algorithm to improve the safety and efficacy of tFUS therapy. The algorithm utilizes pre beamforming DMUA echo data to perform optimal refocusing in multiple frequency bands within the transducer bandwidth based on user selection of the target and any critical points on the skull. The refocusing is performed by computing an improved estimate of propagation operators from the DMUA elements to the selected points, and then substituting the operators in the solution of the optimization problem for refocusing to calculate a refocused array excitation vector. The refocused vector minimizes the incident acoustic power at the critical point while maintaining or increasing the incident power at the target point. In addition, the thesis experimentally demonstrated the feasibility of refocusing tFUS beams at a wideband range of operating frequencies. It also showed that the focusing gain improvement due to refocusing varies non monotonically as a function of frequency. In order to demonstrate this experimentally, we used a set of 32 discrete frequencies that cover the frequency range from 1.9 to 5.0 MHz to generate tFUS beams with and without refocusing. The results clearly demonstrated the need to take the frequency dependence into account in the optimization of transcranial focusing. The results set the stage for the real-time implementation of optimal refocusing using wideband waveforms for improving the speci- city and the localization of the focal region of the beam. In thermal therapy applications, this translates into enhancing the heating e-ciency at the target location and minimizing the exposure over the skull. In neuromodulation applications, this translates into targeting brain circuitry with high degree of speci- city to minimize inadvertent stimulation or inhibition of neural activity in non-targeted regions.
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